TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8239	24940;24941;24942	chr2:178718391;178718390;178718389	chr2:179583118;179583117;179583116
N2AB	7922	23989;23990;23991	chr2:178718391;178718390;178718389	chr2:179583118;179583117;179583116
N2A	6995	21208;21209;21210	chr2:178718391;178718390;178718389	chr2:179583118;179583117;179583116
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-67
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1218
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/T	rs2077819913	None	0.324	N	0.645	0.356	0.224531998449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs2077819913	None	0.324	N	0.645	0.356	0.224531998449	gnomAD-4.0.0	2.02985E-06	None	None	None	None	N	None	3.49394E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.5525	ambiguous	0.5697	pathogenic	-0.708	Destabilizing	0.981	D	0.673	neutral	None	None	None	None	N
A/D	0.5402	ambiguous	0.5513	ambiguous	-1.644	Destabilizing	0.241	N	0.739	prob.delet.	None	None	None	None	N
A/E	0.5854	likely_pathogenic	0.6004	pathogenic	-1.54	Destabilizing	0.324	N	0.709	prob.delet.	N	0.470215198	None	None	N
A/F	0.7104	likely_pathogenic	0.7087	pathogenic	-0.767	Destabilizing	0.932	D	0.803	deleterious	None	None	None	None	N
A/G	0.0798	likely_benign	0.084	benign	-1.29	Destabilizing	None	N	0.352	neutral	N	0.279256619	None	None	N
A/H	0.7133	likely_pathogenic	0.7345	pathogenic	-1.709	Destabilizing	0.818	D	0.804	deleterious	None	None	None	None	N
A/I	0.7217	likely_pathogenic	0.6989	pathogenic	0.062	Stabilizing	0.818	D	0.769	deleterious	None	None	None	None	N
A/K	0.718	likely_pathogenic	0.7455	pathogenic	-1.026	Destabilizing	0.388	N	0.712	prob.delet.	None	None	None	None	N
A/L	0.5165	ambiguous	0.5111	ambiguous	0.062	Stabilizing	0.563	D	0.711	prob.delet.	None	None	None	None	N
A/M	0.5598	ambiguous	0.5585	ambiguous	0.045	Stabilizing	0.981	D	0.756	deleterious	None	None	None	None	N
A/N	0.5191	ambiguous	0.5305	ambiguous	-1.037	Destabilizing	0.008	N	0.59	neutral	None	None	None	None	N
A/P	0.9239	likely_pathogenic	0.9306	pathogenic	-0.217	Destabilizing	0.773	D	0.76	deleterious	N	0.470468688	None	None	N
A/Q	0.5699	likely_pathogenic	0.5925	pathogenic	-0.987	Destabilizing	0.818	D	0.771	deleterious	None	None	None	None	N
A/R	0.5689	likely_pathogenic	0.5982	pathogenic	-0.979	Destabilizing	0.818	D	0.755	deleterious	None	None	None	None	N
A/S	0.0888	likely_benign	0.0915	benign	-1.433	Destabilizing	0.09	N	0.598	neutral	N	0.458351914	None	None	N
A/T	0.1816	likely_benign	0.1882	benign	-1.223	Destabilizing	0.324	N	0.645	neutral	N	0.470215198	None	None	N
A/V	0.424	ambiguous	0.4055	ambiguous	-0.217	Destabilizing	0.492	N	0.654	neutral	N	0.470215198	None	None	N
A/W	0.934	likely_pathogenic	0.9355	pathogenic	-1.428	Destabilizing	0.981	D	0.807	deleterious	None	None	None	None	N
A/Y	0.7726	likely_pathogenic	0.783	pathogenic	-0.881	Destabilizing	0.932	D	0.8	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.